TY - JOUR
T1 - Commensal microbiota enhance both osteoclast and osteoblast activities
AU - Uchida, Yoko
AU - Irie, Koichiro
AU - Fukuhara, Daiki
AU - Kataoka, Kota
AU - Hattori, Takako
AU - Ono, Mitsuaki
AU - Ekuni, Daisuke
AU - Kubota, Satoshi
AU - Morita, Manabu
N1 - Funding Information:
Funding: This work was financially supported by Grants-in-Aid for Scientific Research (nos. 26893304, 16K20694, and 18K17282) from the Ministry of Education, Culture, Sports, Science and Technology, Tokyo, Japan.
Funding Information:
This work was financially supported by Grants-in-Aid for Scientific Research (nos. 26893304, 16K20694, and 18K17282) from the Ministry of Education, Culture, Sports, Science and Technology, Tokyo, Japan. We thank Mika Ikegame, Department of Oral Morphology, for useful suggestions. We also thank Eriko Aoyama, Advanced Research Center for Oral and Craniofacial Sciences, for technical support.
Publisher Copyright:
© 2018 by the authors.
PY - 2018
Y1 - 2018
N2 - Recent studies suggest that the commensal microbiota affects not only host energy metabolism and development of immunity but also bone remodeling by positive regulation of osteoclast activity. However, the mechanism of regulation of bone cells by the commensal microbiota has not been elucidated. In this study, 8-week-old specific pathogen-free (SPF) and germ-free (GF) mice were compared in terms of alveolar bones and primary osteoblasts isolated from calvarias. Micro-CT analysis showed that SPF mice had larger body size associated with lower bone mineral density and bone volume fraction in alveolar bones compared with GF mice. Greater numbers of osteoclasts in alveolar bone and higher serum levels of tartrate-resistant acid phosphatase 5b were observed in SPF mice. Tissue extracts from SPF alveolar bone showed higher levels of cathepsin K, indicating higher osteoclast activity. SPF alveolar extracts also showed elevated levels of γ-carboxylated glutamic acid–osteocalcin as a marker of mature osteoblasts compared with GF mice. Polymerase chain reaction (PCR) array analysis of RNA directly isolated from alveolar bone showed that in SPF mice, expression of mRNA of osteocalcin, which also acts as an inhibitor of bone mineralization, was strongly enhanced compared with GF mice. Cultured calvarial osteoblasts from SPF mice showed reduced mineralization but significantly enhanced expression of mRNAs of osteocalcin, alkaline phosphatase, insulin-like growth factor-I/II, and decreased ratio of osteoprotegerin/receptor activator of nuclear factor-kappa B ligand compared with GF mice. Furthermore, PCR array analyses of transcription factors in cultured calvarial osteoblasts showed strongly upregulated expression of Forkhead box g1. In contrast, Gata-binding protein 3 was strongly downregulated in SPF osteoblasts. These results suggest that the commensal microbiota prevents excessive mineralization possibly by stimulating osteocalcin expression in osteoblasts, and enhances both osteoblast and osteoclast activity by regulating specific transcription factors.
AB - Recent studies suggest that the commensal microbiota affects not only host energy metabolism and development of immunity but also bone remodeling by positive regulation of osteoclast activity. However, the mechanism of regulation of bone cells by the commensal microbiota has not been elucidated. In this study, 8-week-old specific pathogen-free (SPF) and germ-free (GF) mice were compared in terms of alveolar bones and primary osteoblasts isolated from calvarias. Micro-CT analysis showed that SPF mice had larger body size associated with lower bone mineral density and bone volume fraction in alveolar bones compared with GF mice. Greater numbers of osteoclasts in alveolar bone and higher serum levels of tartrate-resistant acid phosphatase 5b were observed in SPF mice. Tissue extracts from SPF alveolar bone showed higher levels of cathepsin K, indicating higher osteoclast activity. SPF alveolar extracts also showed elevated levels of γ-carboxylated glutamic acid–osteocalcin as a marker of mature osteoblasts compared with GF mice. Polymerase chain reaction (PCR) array analysis of RNA directly isolated from alveolar bone showed that in SPF mice, expression of mRNA of osteocalcin, which also acts as an inhibitor of bone mineralization, was strongly enhanced compared with GF mice. Cultured calvarial osteoblasts from SPF mice showed reduced mineralization but significantly enhanced expression of mRNAs of osteocalcin, alkaline phosphatase, insulin-like growth factor-I/II, and decreased ratio of osteoprotegerin/receptor activator of nuclear factor-kappa B ligand compared with GF mice. Furthermore, PCR array analyses of transcription factors in cultured calvarial osteoblasts showed strongly upregulated expression of Forkhead box g1. In contrast, Gata-binding protein 3 was strongly downregulated in SPF osteoblasts. These results suggest that the commensal microbiota prevents excessive mineralization possibly by stimulating osteocalcin expression in osteoblasts, and enhances both osteoblast and osteoclast activity by regulating specific transcription factors.
KW - Bone remodeling
KW - Commensal microbiota
KW - Insulin-like growth factor-1
KW - Osteoblast
KW - Osteocalcin
UR - http://www.scopus.com/inward/record.url?scp=85049405757&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85049405757&partnerID=8YFLogxK
U2 - 10.3390/molecules23071517
DO - 10.3390/molecules23071517
M3 - Article
C2 - 29937485
AN - SCOPUS:85049405757
SN - 1420-3049
VL - 23
JO - Molecules
JF - Molecules
IS - 7
M1 - 1517
ER -